Endogenous Electric Field-Coupled PD@BP Biomimetic Periosteum Promotes Bone Regeneration through Sensory Nerve via Fanconi Anemia Signaling Pathway.

To treat bone defects, repairing the nerve-rich periosteum is critical for repairing the local electric field. In this study, an endogenous electric field is coupled with 2D black phosphorus electroactive periosteum to explore its role in promoting bone regeneration through nerves. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) are used to characterize the electrically active biomimetic periosteum. Here, the in vitro effects exerted by the electrically active periosteum on the transformation of Schwann cells into the repair phenotype, axon initial segment (AIS) and dense core vesicle (DCV) of sensory neurons, and bone marrow mesenchymal stem cells are assessed using SEM, immunofluorescence, RNA-sequencing, and calcium ion probes. The electrically active periosteum stimulates Schwann cells into a neuroprotective phenotype via the Fanconi anemia pathway, enhances the AIS effect of sensory neurons, regulates DCV transport, and releases neurotransmitters, promoting the osteogenic transformation of bone marrow mesenchymal stem cells. Microcomputed tomography and other in vivo techniques are used to study the effects of the electrically active periosteum on bone regeneration. The results show that the electrically active periosteum promotes nerve-induced osteogenic repair, providing a potential clinical strategy for bone regeneration.

Photosensitive and Conductive Hydrogel Induced Innerved Bone Regeneration for Infected Bone Defect Repair.

Repairing infected bone defects is a challenge in the field of orthopedics because of the limited self-healing capacity of bone tissue and the susceptibility of refractory materials to bacterial activity. Innervation is the initiating factor for bone regeneration and plays a key regulatory role in subsequent vascularization, ossification, and mineralization processes. Infection leads to necrosis of local nerve fibers, impeding the repair of infected bone defects. Herein, a biomaterial that can induce skeletal-associated neural network reconstruction and bone regeneration with high antibacterial activity is proposed for the treatment of infected bone defects. A photosensitive conductive hydrogel is prepared by incorporating magnesium-modified black phosphorus (BP@Mg) into gelatin methacrylate (GelMA). The near-infrared irradiation-based photothermal and photodynamic treatment of black phosphorus endows it with strong antibacterial activity, improving the inflammatory microenvironment and reducing bacteria-induced bone tissue damage. The conductive nanosheets and bioactive ions released from BP@Mg synergistically improve the migration and secretion of Schwann cells, promote neurite outgrowth, and facilitate innerved bone regeneration. In an infected skull defect model, the GelMA-BP@Mg hydrogel shows efficient antibacterial activity and promotes bone and CGRP+ nerve fiber regeneration. The phototherapy conductive hydrogel provides a novel strategy based on skeletal-associated innervation for infected bone defect repair.

The Application of Black Phosphorus Nanomaterials in Bone Tissue Engineering.

Recently, research on and the application of nanomaterials such as graphene, carbon nanotubes, and metal-organic frameworks has become increasingly popular in tissue engineering. In 2014, a two-dimensional sheet of black phosphorus (BP) was isolated from massive BP crystals. Since then, BP has attracted significant attention as an emerging nanomaterial. BP possesses many advantages such as light responsiveness, electrical conductivity, degradability, and good biocompatibility. Thus, it has broad prospects in biomedical applications. Moreover, BP is composed of phosphorus, which is a key bone tissue component with good biocompatibility and osteogenic repair ability. Thereby, BP exhibits excellent advantages for application in bone tissue engineering. In this review, the structure and the physical and chemical properties of BP are described. In addition, the current applications of BP in bone tissue engineering are reviewed to aid the future research and application of BP.

Small Intestinal Submucosa Biomimetic Periosteum Promotes Bone Regeneration.

BACKGROUND: Critical bone defects are a significant problem in clinics. The periosteum plays a vital role in bone regeneration. A tissue-engineered periosteum (TEP) has received increasing attention as a novel strategy for bone defect repairs. METHODS: In this experiment, a biomimetic periosteum was fabricated by using coaxial electrospinning technology with decellularized porcine small intestinal submucosa (SIS) as the shell and polycaprolactone (PCL) as the core. In vitro, the effects of the biomimetic periosteum on Schwann cells, vascular endothelial cells, and bone marrow mesenchymal stem cells were detected by a scratch test, an EdU, a tube-forming test, and an osteogenesis test. In vivo, we used HE staining to evaluate the effect of the biomimetic periosteum on bone regeneration. RESULTS: In vitro experiments showed that the biomimetic periosteum could significantly promote the formation of angiogenesis, osteogenesis, and repaired Schwann cells (SCs). In vivo experiments showed that the biomimetic periosteum could promote the repair of bone defects. CONCLUSIONS: The biomimetic periosteum could simulate the structural function of the periosteum and promote bone repair. This strategy may provide a promising method for the clinical treatment of skull bone defects.

Multifunctional hydrogel loaded with 4-octyl itaconate exerts antibacterial, antioxidant and angiogenic properties for diabetic wound repair.

Cutaneous wound healing, especially diabetic wound healing, is a common clinical problem. Reactive oxygen species (ROS) and bacterial infection are two major factors in the induction of oxidative stress and inflammation, leading to impeded angiogenesis and wound healing. However, it is still very difficult to reverse the harsh microenvironment of chronic inflammation and excessive oxidative stress on diabetic wound. Itaconate, an endogenous metabolite, has recently attracted extensive attention as a critical immune-regulator. In this study, we used 4-octyl itaconate (4OI), a cell-permeable itaconate derivative, to have antioxidative and anti-inflammatory functions for diabetic wound regeneration. Simultaneously, an injectable, self-healing, and antibacterial dynamic coordinative hydrogel was manufactured by binding the 4-arm polyethylene glycol (PEG) with silver nitrate to deliver the bioactive molecule. In vitro experiments confirmed that 4OI@PEG hydrogel could inhibit bacterial growth, protect human umbilical vein endothelial cells from ROS damage and enhance neovascularization. In addition, the hydrogel increased mitochondrial polarization and reduced mitochondrial fragmentation by activating the Keap1-Nrf2 antioxidant defense system. In vivo experiments proved that this multifunctional hydrogel facilitated diabetic wound healing by inhibiting local inflammation and promoting angiogenesis. Collectively, 4OI-loaded multifunctional materials could reverse various unfavorable microenvironments, such as excessive oxidative stress, inflammation, and infection, and can promote neovascularization; thus, such materials show great promise for the treatment of diabetic ulcers.

Assessment of acute traumatic cervical spinal cord injury using conventional magnetic resonance imaging in combination with diffusion tensor imaging-tractography: a retrospective comparative study.

PURPOSE: The application of conventional magnetic resonance imaging (MRI) in combination with diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) to diagnose acute traumatic cervical SCI has not been studied. This study explores the role of MRI with DTI-DTT in the diagnosis of acute traumatic cervical spinal cord injury (SCI). METHODS: Thirty patients with acute traumatic cervical SCI underwent conventional MRI and DTI-DTT. Conventional MRI was used to detect the intramedullary lesion length (IMLL) and intramedullary hemorrhage length (IMHL). DTI was used to detect the spinal cord's fractional anisotropy (FA) and apparent diffusion coefficient value, and DTT detected the imaginary white matter fiber volume and the connection rates of fiber tractography (CRFT). Patients' neurological outcome was determined using the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades. RESULTS: Patients were divided into group A (without AIS grade conversion) and group B (with AIS grade conversion). The IMLL and IMHL of group A were significantly higher than those of group B. The FA and CRFT of group A were significantly lower than those of group B. The final AIS grade was negatively correlated with the IMLL and IMHL, and positively correlated with the FA and CRFT. According to imaging features based on conventional MRI and DTI-DTT, we propose a novel classification and diagnostic procedure. CONCLUSIONS: The combination of conventional MRI with DTI-DTT is a valid diagnostic approach for SCI. Lower IMLL and IMHL, and higher FA value and CRFT are linked to better neurological outcomes.

Bioinspired Multifunctional Black Phosphorus Hydrogel with Antibacterial and Antioxidant Properties: A Stepwise Countermeasure for Diabetic Skin Wound Healing.

Cutaneous wound healing, especially diabetic wound healing, is a common clinical challenge. Reactive oxygen species (ROS) and bacterial infection are two major detrimental states that induce oxidative stress and inflammatory responses and impede angiogenesis and wound healing. A derivative of the metabolite itaconate, 4-octyl itaconate (4OI) has attracted increasing research interest in recent years due to its antioxidant and anti-inflammatory properties. In this study, 4OI-modified black phosphorus (BP) nanosheets are incorporated into a photosensitive, multifunctional gelatin methacrylamide hydrogel to produce a new photothermal therapy (PTT) and photodynamic therapy (PDT) system with antibacterial and antioxidant properties for diabetic wound regeneration. Under laser irradiation, the 4OI-BP-entrapped hydrogel enables rapid gelation, forming a membrane on wounds, and offers high PTT and PDT efficacy to eliminate bacterial infection. Without laser irradiation, BP acts as a carrier and controls the release of 4OI, with which it synergistically enhances antioxidant activity, thus alleviating excessive ROS damage to endothelial cells, promoting neovascularization, and facilitating faster diabetic wound closure. These findings indicate that 4OI-BP-entrapped multifunctional hydrogel provides a stepwise countermeasure with antibacterial and antioxidant properties for enhanced diabetic wound healing and may lead to novel therapeutic interventions for diabetic ulcers.

Treatment of Upper Cervical Spinal Cord Injury (Unstable C1-C2) by Direct Visualization and Nailing Technique and the Advantages of Early MRI.

Background: The treatment of C1-C2 fractures mainly depends on fracture type and the stability of the atlantoaxial joint. Disruption of the C1-C2 combination is a big challenge, especially in avoiding vertebral artery, nerve, and vein sinus injury during the operation. Purpose: This study aims to show the benefit of using the posterior approach and pedicle screw insertion by nailing technique and direct visualization to treat unstable C1-C2 and, moreover, to determine the advantages of performing early MRI in patients with limited neck movement after trauma. Method: Between Jan 2017-Feb 2019, we present 21 trauma patients who suffered from C1, C2, or unstable atlantoaxial joint. X-ray, computed tomography (CT), and magnetic resonance image (MRI) were performed preoperatively. All the patients underwent our surgical procedure (posterior approach and pedicle screw placement by direct visualization and nailing technique). Result: The mean age was 41.1 years old, 8 females and 14 males. The average follow-up time was 2.6 years. Four patients were with C1 fracture, seven with C2 fracture, six with atlantoaxial dislocation, and four with C1 and C2 fractures. The time of MRI was between 12 hours and 48 hours; neck movement symptoms appeared between 2 days and 2 weeks. Conclusion: The posterior approach to treat the C1 and C2 fractures or dislocation by direct visualization and nailing technique can reduce the risk of the vertebral artery, vein sinus, and nerve root injuries with significant improvement. It can show a better angle view while inserting the pedicle screws. An early MRI (12-48 hours) is essential even if no symptoms appear at the time of admission, and if it is normal, it is necessary to repeat it. The presence of skull bleeding can be associated with upper neck instability.

Medical Communication Services after Traumatic Spinal Cord Injury.

It is difficult to assess and monitor the spinal cord injury (SCI) because of its pathophysiology after injury, with different degrees of prognosis and various treatment methods, including laminectomy, durotomy, and myelotomy. Medical communication services with different factors such as time of surgical intervention, procedure choice, spinal cord perfusion pressure (SCPP), and intraspinal pressure (ISP) contribute a significant role in improving neurological outcomes. This review aims to show the benefits of communication services and factors such as ISP, SCPP, and surgical intervention time in order to achieve positive long-term outcomes after an appropriate treatment method in SCI patients. The SCPP was found between 90 and 100 mmHg for the best outcome, MAP was found between 110 and 130 mmHg, and mean ISP is ≤20 mmHg after injury. Laminectomy alone cannot reduce the pressure between the dura and swollen cord. Durotomy and duroplasty considered as treatment choices after severe traumatic spinal cord injury (TSCI).

Evaluating the Severity and Prognosis of Acute Traumatic Cervical Spinal Cord Injury: A Novel Classification Using Diffusion Tensor Imaging and Diffusion Tensor Tractography.

STUDY DESIGN: Retrospective observational cohort study. OBJECTIVE: We explored the relationship between diffusion tensor imaging (DTI) parameters and prognosis in patients with acute traumatic cervical spinal cord injury (ATCSCI). SUMMARY OF BACKGROUND DATA: DTI has been used to diagnose spinal cord injury; nevertheless, its role remains controversial. METHODS: We analyzed retrospectively 24 patients with ATCSCI who were examined using conventional T2-weighted imaging and DTI. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were recorded at the injured site. Diffusion tensor tractography (DTT) was used to measure the spinal cord white matter fiber volume (MWFV). American Spinal Injury Association (ASIA) grades were recorded. Correlations between DTI parameters and ASIA scores were evaluated using Spearman correlation coefficients. RESULTS: FA values at injured sites were significantly lower than those of the control group, whereas ADC values in injured and control groups were not significantly different. DTT revealed that ATCSCI could be divided into four types: Type A1-complete rupture of spinal cord white matter fiber (MWF); Type A2-partial rupture of MWF; Type B-most MWF retained with severe compression or abnormal fiber conduction direction; and Type C-MWF basically complete with slight compression. Preoperative physical examinations revealed complete injury (ASIA A) in patients with A1 (n = 4) and A2 (n = 4). The ASIA grades or scores of A2 were improved to varying degrees, whereas there was no significant improvement in A1. FA values and MWFV of ASIA B, C, and D were significantly higher than those of ASIA A. FA and MWFV were correlated with ASIA motor score preoperatively and at final follow-up. CONCLUSION: We propose a classification for the severity of ATCSCI based on DTI and DTT that may explain why some patients with ASIA A recover, whereas others do not.Level of Evidence: 4.

Magnesium-based materials in orthopaedics: material properties and animal models.

As a new generation of medical metal materials, degradable magnesium-based materials have excellent mechanical properties and osteogenic promoting ability, making them promising materials for the treatment of refractory bone diseases. Animal models can be used to understand and evaluate the performance of materials in complex physiological environments, providing relevant data for preclinical evaluation of implants and laying the foundation for subsequent clinical studies. To date, many researchers have studied the biocompatibility, degradability and osteogenesis of magnesium-based materials, but there is a lack of review regarding the effects of magnesium-based materials in vivo. In view of the growing interest in these materials, this review briefly describes the properties of magnesium-based materials and focuses on the safety and efficacy of magnesium-based materials in vivo. Various animal models including rats, rabbits, dogs and pigs are covered to better understand and evaluate the progress and future of magnesium-based materials. This literature analysis reveals that the magnesium-based materials have good biocompatibility and osteogenic activity, thus causing no adverse reaction around the implants in vivo, and that they exhibit a beneficial effect in the process of bone repair. In addition, the degradation rate in vivo can also be improved by means of alloying and coating. These encouraging results show a promising future for the use of magnesium-based materials in musculoskeletal disorders.

Paroxysmal Laryngospasm: A Rare Condition That Respiratory Physicians Must Distinguish from Other Diseases with a Chief Complaint of Dyspnea.

Background: In recent years, we have observed respiratory difficulty manifested as paroxysmal laryngospasm in a few outpatients, most of whom were first encountered in a respiratory clinic. We therefore explored how to identify and address paroxysmal laryngospasm from the perspective of respiratory physicians. Methods: The symptoms, characteristics, auxiliary examination results, treatment, and prognosis of 12 patients with paroxysmal laryngospasm treated in our hospital from June 2017 to October 2019 were analyzed. Results: Five males (42%) and 7 females (58%) were among the 12 Han patients sampled. The average age of the patients was 49.25 ± 13.02 years. The disease course ranged from 14 days to 8 years and was characterized by sudden dyspnea, an inability to inhale and exhale, a sense of asphyxia, and voice loss during an attack. Eight patients with gastroesophageal reflux were cured after antacid treatment. One case of upper respiratory tract infection (URI) was completely relieved after symptomatic treatment. One patient with left vocal cord paralysis experienced complete relief after specialist treatment by an otorhinolaryngologist. Episodes in 1 patient were significantly reduced after lifestyle improvement. One patient experienced spontaneous relief after rejecting treatment. Conclusions: Paroxysmal laryngospasm is a rare laryngeal disease that generally occurs secondary to gastroesophageal reflux disease (GERD), and antireflux therapy is frequently effective for its treatment. A respiratory physician should master and identify the symptoms and differentiate this condition from hysterical stridor, reflux-related laryngospasm, and asthma. Timely referral to otolaryngologists, gastroenterologists, and other specialists for standardized examination and regular treatment should be provided when necessary.